Vukovic Jovana, Abazovic Dzihan, Vucetic Dusan, Medenica Sanja
Institute for the Application of Nuclear Energy - INEP, University of Belgrade, Belgrade, Serbia.
Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Front Med (Lausanne). 2024 Oct 10;11:1447147. doi: 10.3389/fmed.2024.1447147. eCollection 2024.
CAR-T therapy has demonstrated great success in treating hematological malignancies, which has led to further research into its potential in treating other diseases. Autoimmune diseases have great potential to be treated with this therapy due to the possibility of specific targeting of pathological immune cells and cells that produce autoantibodies, which could lead to permanent healing and restoration of immunological tolerance. Several approaches are currently under investigation, including targeting and depleting B cells via CD19 in the early stages of the disease, simultaneously targeting B cells and memory plasma cells in later stages and refractory states, as well as targeting specific autoantigens through the chimeric autoantibody receptor (CAAR). Additionally, CAR-engineered T regulatory cells can be modified to specifically target the autoimmune niche and modulate the pathological immune response. The encouraging results from preclinical studies have led to the first successful use of CAR-T therapy in humans to treat autoimmunity. This paved the way for further clinical studies, aiming to evaluate the long-term safety and efficacy of these therapies, potentially revolutionizing clinical use.
嵌合抗原受体T细胞(CAR-T)疗法在治疗血液系统恶性肿瘤方面已取得巨大成功,这促使人们进一步研究其在治疗其他疾病方面的潜力。由于有可能特异性靶向病理性免疫细胞和产生自身抗体的细胞,自身免疫性疾病具有采用这种疗法进行治疗的巨大潜力,这可能会带来永久性治愈并恢复免疫耐受。目前正在研究几种方法,包括在疾病早期通过CD19靶向并清除B细胞,在疾病后期和难治性状态下同时靶向B细胞和记忆浆细胞,以及通过嵌合自身抗体受体(CAAR)靶向特定自身抗原。此外,可以对CAR工程化的调节性T细胞进行改造,以特异性靶向自身免疫微环境并调节病理性免疫反应。临床前研究取得的令人鼓舞的结果已促成CAR-T疗法首次成功用于人类自身免疫性疾病的治疗。这为进一步的临床研究铺平了道路,旨在评估这些疗法的长期安全性和有效性,可能会给临床应用带来变革。